Guilherme Nader, PhD
My lab seeks to reconstitute the complex interface between mechanical and chemical signaling in the context of cell migration in complex microenvironments and tissue crowding. When cells grow or move within dense microenvironments their nuclei are subjected to different degrees of deformation. We investigate the mechanisms underlying cell behavior and fate in scenarios where cells experience mechanical stress. We combine several fluorescent microscopy approaches with microfluidics, microfabrication techniques and organ-on-a chip devices to apply controlled and precise confinement to cultured cells and impose different degrees of mechanical stress to their nuclei.
Selected publications:
- DNA damage induces nuclear envelope rupture through ATR-mediated phosphorylation of Lamin A/C. Kovacs, M.T., Vallette, M., Wiertsema, P., Nader, G.P.F., Piel, M., Ceccaldi, R. Mol. Cell. 2023, October; 83: 1-10.
- De Silva, N.S., Siewiera, J., Alkhoury, C., Nader, G.P.F., Nadalin, F., Kevin de Azevedo, Mickaël Couty, Fernández, H.I., Bhargava, A., Conrad, C., Maurin, M., Antoniadou, K., Fouillade, C., Londono-Vallejo, A., Behrendt, R., Bertotti, K., Serdjebi, C., Lanthiez, F., Gallwitz, L., Saftig, P., Fernández, H.B., Saez, A., González-Granado, J.M., van Niel, G., Boissonnas, A., Piel, M., Manel, N. Nuclear envelope disruption triggers hallmarks of aging in lung alveolar macrophages. Nature Aging. 2023, September; 3: 1251–68.
- Frittoli, E., Palamidessi, A., Iannelli, F., Zanardi, F., Villa, S., Barzaghi, L., Abdo, H., Cancila, V., Beznoussenko, G. V., Della Chiara, G., Pagani, M., Malinverno, C., Bhattacharya, D., Pisati, F., Yu, W., Galimberti, V., Bonizzi, G., Martini, E., Mironov, A. A., Gioia, U., Ascione, F., Li, Q., Havas, K., Magni, S., Lavagnino, Z., Pennacchio, F. A., Maiuri, P., Caponi, S., Mattarelli, M., Martino, S., d'Adda di Fagagna, F., Rossi, C., Lucioni, M., Tancredi, R., Pedrazzoli, P., Vecchione, A., Petrini, C., Ferrari, F., Lanzuolo, C., Bertalot, G., Nader, G.P.F., Foiani, M., Piel, M., Cerbino, R., Giavazzi, F., Tripodo, C., & Scita, G. Tissue fluidification promotes a cGAS-STING cytosolic DNA response in invasive breast cancer. Nature Materials. 2022, May; 22: 644-655.
- Nader, G.P.F., Agüera-Gonzalez, S., Routet, F., Gratia, M., Maurin, M., Cancila, V., Cadart, C., Palamidessi, A., Ramos, R.N., San Roman, M., Gentili, M., Yamada, A., Williart, A., Lodillinsky, C., Lagoutte, E., Villard, C., Viovy, J-L., Tripodo, C., Scita, G., Manel, N., Chavrier, P., Piel, M. Compromised nuclear envelope integrity drives TREX1-dependent DNA damage and tumor cell invasion. Cell. 2021, September; 184: 1-17.
- Nader, G.P.F., Williart, A. & Piel, M. Nuclear deformations, from signaling to perturbation and damage. Current Opinion in Cell Biology. 2021, August; 72: 137–145.
- Srivastava, N., Nader, G.P.F.*, Williart, A., Rollin, R., Cuvelier, D., Lomakin, A., Piel, M. Nuclear fragility, blaming the Blebs. Current Opinion in Cell Biology. 2021, March; 70: 100-108. doi:10.1016/j.ceb.2021.01.007. *Co-first author.
- Lomakin, A.J., Cattin, C.J., Cuvelier, D., Alraies, Z., Molina, M., Nader, G.P.F, Srivastava, N., Saez, P.J., Garcia-Arcos, J.M., Zhitnyak, I.Y., Bhargava, A., Driscoll, M.K., Welf, E.S., Fiolka, R., Petrie, R.J., De Silva, N.S., González-Granado, J. M., Manel, N., Lennon-Duménil, A.M., Müller, D.J., Piel, M. The nucleus acts as a ruler tailoring cell responses to spatial constraints. Science. 2020, October; 370, eaba2894.
- Gentili, M., Lahaye, X., Nadalin, F., Nader, G.P.F., Puig Lombardi, E., Herve, S., De Silva, N.S., Rookhuizen, D.C., Zueva, E., Goudot, C., Maurin, M., Bochnakian A., Amigorena, S., Piel, M., Fachinetti, D., Londono-Vallejo, A. and Manel, N. The N-terminal domain of cGAS determines preferential association with centromeric DNA and innate immune activation in the nucleus. Cell Reports. 2019, February, 2377–93.
- Nader, G.P.F., Ezratty, E.J and Gundersen, G.G. FAK, talin and PIPKIγ regulate endocytosed integrin conformation to polarize focal adhesion assembly. Nature Cell Biology. 2016, May; 18(5): 491-503.